Glycogen synthase kinase-3 (GSK-3), a proline-directed, serine/threonine kinase for which two isoforms; GSK-3α and GSK-3β, have been identified, phosphorylates the rate-limiting enzyme of glycogen synthesis, glycogen synthase (GS). See, for example, Embi, et al., Eur. J. Biochem., 107, 519–527 (1980). GSK-3α and GSK-3β are both highly expressed in the body. See, for example, Woodgett, et al., EMBO, 9, 2431–2438 (1990) and Loy, et al., J. Peptide Res., 54, 85–91 (1999). Besides GS, a number of other GSK-3 substrates have been identified, including many metabolic, signaling, and structural proteins. Notable among the plurality of signaling proteins regulated by GSK-3 are many transcription factors, including activator protein-1; cyclic AMP response element binding protein (CREB); the nuclear factor (NF) of activated T-cells; heat shock factor-1; β-catenin; c-Jun; c-Myc; c-Myb; and NF-KB. See, for example, C. A. Grimes, et al., Prog. Neurobiol., 65, 391–426 (2001), H. Eldar-Finkelman, Trends in Molecular Medicine, 8, 126–132 (2002), and P. Cohen, et al., Nature, 2, 1–8, (2001). Accordingly, targeting the activity of GSK-3 has significant therapeutic potential in the treatment of many disparate pathologies and conditions, for example, Alzheimer's Disease (A. Castro, et al., Exp. Opin. Ther. Pat., 10, 1519–1527 (2000)); asthma (P. J. Barnes, Ann. Rev. Pharmacol. Toxicol., 42, 81–98 (2002)); cancer (Beals, et al., Science, 275, 1930–1933 (1997), L. Kim, et al., Curr. Opin. Genet. Dev., 10, 508–514 (2000), and Q. Eastman, et al., Curr. Opin. Cell Biol., 11, 233 (1999)); diabetes and its related sequelae, for example, Syndrome X and obesity (S. E. Nikoulina, et al., Diabetes, 51, 2190–2198 (2002), Orena, et al., JBC, 15765–15772 (2000), and Summers, et al., J. Biol. Chem., 274 17934–17940 (1999)); hair loss (S. E. Millar, et al., Dev. Biol., 207, 133–149 (1999) and E. Fuchs, et al., Dev. Cell, 1, 13–25 (2001)); inflammation (P. Cohen, Eur. J. Biochem., 268, 5001–5010 (2001)); mood disorders, such as depression (A. Adnan, et al., Chem. Rev., 101, 2527–2540 (2001) and R. S. B. Williams, et al., Trends Phamacol. Sci., 21, 61–64 (2000)); neuronal cell death and stroke (D. A. E. Cross, et al., J. Neurochem., 77, 94–102 (2001) and C. Sasaki, et al., Neurol. Res., 23, 588–592 (2001)); bipolar disorder (Klein, et al., PNAS, 93, 8455–8459 (1996)); skeletal muscle atrophy (G. J. Brunn, et al., Science, 277, 99–101 (1997), R. E. Rhoads, J. Biol. Chem., 274, 30337–30340 (1999), V. R. Dharmesh, et al., Am. J. Physiol. Cell Physiol. 283, C545–551 (2002), and K. Baar, et al., A. J. Physiol., 276, C120–C127 (1999)); decreased sperm motility (Vijayaraghavan, et al., Biol. Reproduction, 54, 709–718 (1996)); and in cardio-protection (C. Badorff, et al., J. Clin. Invest., 109, 373–381 (2002), S. Haq, et al., J. Cell Biol., 151, 117–129 (2000), and H. Tong, et al., Circulation Res., 90, 377–379 (2002)).